Synthesis of New Functionalized Organocopper Reagents via a Halogen-Copper Exchange Reaction

Highly functionalized organometallic compounds are key
intermediates for the preparation of polyfunctionalized molecules.
Halogen-metal exchange reaction is a general and chemoselective
method for preparing functionalized organometallics, such as
organolithium or organomagnesium. However, more sensitive
functionalities, such as ketones and aldehydes are usually not
compatible with these reagents. To overcome these problems, we
developed a halogen-copper exchange reaction by using two
sterically hindered lithium dialkylcuprates, which allowed a
practical preparation of functionalized lithium cuprate reagents.
Various functionalized cuprate reagents were prepared by using this
method like functionalized aryl, heteroaryl and alkenyl cuprate
reagents. A wide range of functional groups were tolerated by this
method, such as ketones, esters, cyanide, halides, methoxyl group,
or even aldehyde. The resulting functionalized copper reagents
reacted readily with various electrophiles leading to highly
functionalized molecules. The application of functionalized aryl
cuprates obtained via I/Cu-exchange reaction in stereoselective
allylic substitution reaction was also described. Finally, a
related new method was developed for the preparation of
polyfunctional magnesium arylcuprates obtained by an I/Cu-exchange
reaction. Especial interest was that the reaction proceeded in a
very clean way with the only side-product cyclopentane. Various
functionalized organocopper reagents were obtained by this new
method.